Neutrophil Infiltration Is Partially Inhibited By EC-18 in the LPS-Induced Acute Lung Injury

Acute lung injury (ALI) is an acute respiratory failure and linked closely to neutrophil accumulation. It can lead to acute respiratory distress syndrome (ARDS). Mouse model of ALI was established by lipopolysaccharide (LPS) administration. LPS, an outer membrane of gram negative bacteria, is considered as immune stimulator via recognition as pathogen-associated molecular patterns (PAMP). ALI and neutrophil infiltration were readily induced by intranasal injection of LPS. In this study, we investigated whether EC-18 treatment attenuates LPS-induced ALI. EC-18 (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is an immune modulator in the allergic asthma response through modulation of the balance between Th1 and Th2. To analyze the role of EC-18 in LPS-induced ALI mice, Balb/c mice were divided into three separate groups: control, LPS treated, and EC-18/LPS co-treated (n=5 per group). 25 mg/kg of LPS was administered by an intranasal route, and 250 mg/kg of EC-18 was orally administered. Mice were sacrificed after 15hrs, and various samples were collected. Bone marrow cells, whole blood cells, cells in lung and bronchoalveolar lavage fluid (BALF) were analyzed using complete blood count (CBC) assay. As results, the number of neutrophil in the bone marrow was decreased in the LPS treated group, and the circulating neutrophil, neutrophil in the lung and BALF were significantly increased in the LPS treated group. Neutrophils in the lung and BALF were dramatically decreased in the EC-18/LPS co-treated group. Also, Evans Blue staining of the lung indicated that capillary permeability was enhanced in the LPS injected mice, and this permeability was lessened in the EC-18/LPS co-treated group as much as that of control. These findings suggested that EC-18 could effectively block neutrophil transmigration into the lung and vesicular leakage. Consequently, EC-18 could be utilized as a potential therapeutic agent for acute and chronic inflammation related disease like ALI.